Search

`Are we alone?' The Search for Extra-Terrestrial Intelligence (SETI) aims to answer this profound question. Apart from examining environments in our solar system and detecting biosignatures in exoplanet atmospheres, SETI is another main approach to search for life beyond Earth by detecting technosignatures indicative of extra-terrestrial intelligence (ETI), such as engineering radio signals. Massive efforts have been made by SETI scientists using radio telescopes around the world. Though some candidate signals were detected, none of them has been confirmed as an ETI technosignature so far. Most targeted SETI observations performed in recent years use on-off strategy to distinguish signals transmitted from celestial bodies from radio frequency interference (RFI) generated near the ground. Here we report a SETI campaign employing another SETI observation strategy, multi-beam coincidence matching (MBCM), at the Five-hundred-meter Aperture Spherical radio Telescope (FAST) towards 33 currently discovered planetary systems, searching for narrow band drifting signals at a band of $1.05-1.45$ GHz. Our observations achieve an unprecedented sensitivity with a minimum Equivalent Isotropic Radiated Power (EIRP) of $1.5 \times 10^{9} ~\text{W}$. We process the data of two orthogonal polarization separately, aiming to discriminate instrumental RFI signals. A particular signal at 1140.604 MHz from the observation towards Kepler-438 passes our initial selection criteria. Although we have not yet determined the exact cause of this signal, its polarization characteristic suggests that it is most likely to be attributed to RFI. In spite of this, our work verifies that compared to single-beam on-off strategy, MBCM greatly improves both time efficiency and radio frequency interference (RFI) identification effectiveness of targeted SETI observations.

Hai Yan Zhang,1 Mei Chan Chong,1 Maw Pin Tan,2 Yan Piaw Chua,3 Jin Hua Zhang4 1Department of Nursing Science, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; 2Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; 3Department of Mathematics and Science Education, Faculty of Education, University of Malaya, Kuala Lumpur, Malaysia; 4Faculty of Nursing, Xin Xiang Medical University, Xin Xiang City, People’s Republic of ChinaCorrespondence: Mei Chan Chong, Department of Nursing Science, Faculty of Medicine, University of Malaya, Kuala Lumpur, 50603, Malaysia, Tel +603-79492806, Email mcchong@um.edu.my Jin Hua Zhang, Faculty of Nursing, Xin Xiang Medical University, Xin Xiang City, 453000, People’s Republic of China, Tel +86-13837328062, Email zjh.warm@163.comPurpose: To evaluate the relationship between depressive symptoms and sarcopenia among older adults.Materials and Methods: This is a cross-sectional study. A total of 700 community-dwelling older persons enrolled in this study. Sarcopenia is defined according to the Asian Working Group for Sarcopenia 2019 (AWGS 2019). The bioelectrical impedance analysis assessed muscle mass while a digital dynamometer quantified muscle strength. Furthermore, a 6-meter gait speed test measured physical performance. The Geriatric Depression Scale (GDS-30) screened for depressive symptoms. Data collected include those of socio-demographic, lifestyle, and comorbidity.Results: The sample comprised 700 participants (455 women) with a mean age of 70.4± 6.8 years. 21.5% had sarcopenia, among them, 5.6% at severe stage, while depressive symptoms were present in 8.1% (57/700). After adjusting for the potential confounders of age, sex, marital status, living status, hypertension, body mass index, and physical activity, the depressive symptoms that were found were not associated with sarcopenia but, instead, low gait speed. However, severe sarcopenia significantly impacted the risk of depressive symptoms, particularly in females.Conclusion: Depressive symptoms are not associated with sarcopenia, but severe sarcopenia increases the risk of depressive symptoms in females, according to updated AWGS 2019 criteria. Gait speed is independently associated with depressive symptoms. The finding highlights that older people with sarcopenia should be screened for depressive symptoms, especially females. Future studies should evaluate the value of gait speed interventions for depressive symptoms among older adults.Keywords: depressive symptoms, sarcopenia, older people

As a major approach to looking for life beyond the Earth, the search for extraterrestrial intelligence (SETI) is committed to detecting technosignatures such as engineered radio signals that are indicative of technologically capable life. In this paper, we report a targeted SETI campaign employing an observation strategy named multi-beam coincidence matching (MBCM) at the Five-hundred-meter Aperture Spherical radio Telescope (FAST) towards 33 known exoplanet systems, searching for ETI narrow-band drifting signals across 1.05-1.45 GHz in two orthogonal linear polarization directions separately. A signal at 1140.604 MHz detected from the observation towards Kepler-438 originally peaked our interest because its features are roughly consistent with assumed ETI technosignatures. However, evidences such as its polarization characteristics are almost able to eliminate the possibility of an extraterrestrial origin. Our observations achieve an unprecedented sensitivity since the minimum equivalent isotropic radiated power (EIRP) we are able to detect reaches 1.48 x10^9 W., Comment: 17 pages, 12 figures, matches the published version

This study sought to determine whether mesenchymal stem cells-derived extracellular vesicles (MSCs-EVs) carrying microRNA-378a-3p (miR-378a-3p) could affect the pathogenesis of inflammatory bowel disease (IBD) by regulating the GATA-binding protein 2 (GATA2)/aquaporin-4 (AQP4)/peroxisome proliferator-activated receptor α (PPAR-α) axis. Initially, colon mucosa biopsy tissues were harvested from healthy controls and patients with IBD for qRT-PCR and immunohistochemistry analysis. EVs harvested from MSCs and lipopolysaccharide (LPS) were used to stimulate the M064 cells to establish an in vitro inflammation cell model. Besides, 2,4,6-trinitrobenzene sulfonic acid intracolon administration was performed to establish in vivo IBD mouse models. After loss- and gain-of-function assays, the regulatory role of MSCs-derived EVs loaded with manipulated miR-378a-3p in IBD in relation to GATA2/AQP4/PPAR-α were explored. Upregulation of GATA2 was identified in the colon tissue of IBD patients. GATA2, which was a target gene of miR-378a-3p, transcriptionally upregulated AQP4. After silencing of GATA2, LPS-induced apoptosis of M064 cells was reduced by the downregulation of AQP4. Decreased AQP4 contributed to PPAR-α pathway inactivation and weakened the LPS-induced apoptosis of M064 cells. MSCs-EVs delivering miR-378a-3p suppressed the GATA2/AQP4/PPAR-α pathway, which reduced LPS-induced apoptosis of M064 cells and the occurrence of IBD in mice. Altogether, the current study illustrated that MSCs-EVs transfer miR-378a-3p to reduce the GATA2 expression, which downregulates AQP4 to block the PPAR-α signalling pathway, thus suppressing the occurrence of IBD.

The discovery of new therapeutic agents for ischemic stroke remains an urgent need. Here, we identified a novel phenyl carboxylic acid derivative, n-pentyl 4-(3,4-dihydroxyphenyl)-4-oxobutanoate (PDPOB), with anti-ischemic activities. The in vitro anti-ischemic neuroprotective and anti-inflammatory capacities of PDPOB were investigated using neuronal cells suffering from oxygen-glucose deprivation/reperfusion (OGD/R) and microglial cells stimulated by lipopolysaccharide (LPS). PDPOB attenuated the OGD/R-evoked cellular damage of SH-SY5Y cells and primary cortical neurons in a concentration-dependent manner. Likewise, PDPOB displayed protective roles against OGD/R-evoked multiaspect neuronal deterioration in SH-SY5Y cells, as evidenced by alleviated mitochondrial dysfunction, oxidative stress, and apoptosis. A further study unveiled the accelerated phosphorylation of protein kinase B (AKT) by PDPOB treatment, while blockade of phosphoinositide 3-kinase (PI3K)/AKT signaling substantially diminished the neuroprotective capacities of PDPOB. Additionally, the PDPOB pretreatment dampened the LPS-evoked neuroinflammation in BV2 cells, characterized by the suppressed secretion of nitric oxide (NO) and proinflammatory cytokines, as well as normalized expression of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Western blotting further revealed that PDPOB abated the overabundant phosphorylation of the extracellular signal-regulated kinase (ERK), c-Jun-N-terminal kinase (JNK), and p38 in LPS-exposed BV2 cells. The intravenous application of PDPOB (30 mg/kg, single dose) attenuated ipsilateral cerebral infarction in middle cerebral artery occlusion (MCAO) rats, accompanied by recovered neurological behaviors. Collectively, the above observations provided substantial evidence for the favorable properties and mechanistic explanations of PDPOB in the regulation of ischemia-associated neuronal injury and microglial inflammation, which may furnish ideas for the discovery of new therapeutic strategies against cerebral ischemia.

Laryngeal squamous cell carcinoma (LSCC) is the most common malignant tumor in the head and neck cancer, with a poor prognosis. As we know, microRNAs (miRNAs) play a vital role in the initiation and development of various cancers including LSCC. In this study, we explored the role of miR-125b-5p and its downstream regulatory pathway in LSCC. Our data demonstrated that miR-125b-5p expression was significantly downregulated in LSCC tissues and cells. LSCC patients with high expression of miR-125b-5p had higher overall survival (OS) and were closely related to the clinical stage. Overexpression of miR-125b-5p impaired viability and glycolysis, and facilitated apoptosis in LSCC cells. And miR-125b-5p silencing had the opposite effects. Bioinformatics website predicted that MAP3K9 was one of the potential target genes of miR-125b-5p. Cell experiments demonstrated that miR-125b-5p repressed the MAP3K9 levels by directly targeting MAP3K9. Additionally, the negative correlation between miR-125b-5p and MAP3K9 was validated in LSCC tissues. Overexpression of MAP3K9 attenuated the inhibitory effect of miR-125b-5p on viability and glycolysis, and the pro-apoptosis effect of miR-125b-5p in LSCC cells. Furthermore, in vivo experiments demonstrated that tumor growth was hampered in AMC-HN-8 cells transfected with miR-125b-5p mimic. In contrast, the knockdown of miR-125b-5p reduced tumor growth in vivo. Meanwhile, the in vivo immunohistochemistry and TUNEL assays suggested that the miR-125b-5p overexpression restrained cell proliferation and promoted apoptosis via targeting MAP3K9. Overall, these above results suggested that miR-125b-5p suppressed proliferation and glycolysis, and promoted apoptosis by directly targeting MAP3K9 in LSCC cells. Thus, miR-125b-5p acts as a tumor suppressor miRNA and the miR-125b-5p/MAP3K9 axis may be a promising candidate for LSCC treatment.

A novel diterpenoid, sinunanolobatone A (1), featuring an unprecedented bicyclo[13.1.0]pentadecane carbon framework, along with two new casbane diterpenoids (2 and 3), and five known related ones (4-8) were isolated from the Sanya soft coral Sinularia nanolobata. The structures of the new compounds were established by detailed spectroscopic analysis, X-ray diffraction analysis, chemical reactions, or a quantum chemical computation method. A plausible biosynthetic pathway of 1 was proposed. In bioassay, the novel compound 1 showed significant inhibitory activity against lipopolysaccharide (LPS) induced inflammation in BV-2 microglial cells.

The molecular mechanisms underlying allelopathy and their role in the interactions between invasive weeds and native species remain unclear. In this study, we aimed to explore the physiological and molecular response of plant roots of a native species to allelopathy from an invasive weed. We examined the growth and development of roots of native Arabidopsis thaliana for a 2-week period after being treated with aqueous extracts at different concentrations from invasive Conyza canadensis. Extracts with higher concentration in the Murashige and Skoog (MS) media (i.e., 4 mg of extract/mL of MS) significantly affected the root growth of A. thaliana. Roots of A. thaliana displayed weakened root tip activity and an accumulation of reactive oxygen species (ROS) in response to extracts from C. canadensis. The transcriptome analysis of A. thaliana roots exposed to phytotoxicity revealed differentially expressed genes (DEGs) involved in cell wall formation, abiotic stress, transporter genes and signal transduction. We found that genes associated with nutrient transport, such as major facilitator superfamily (MFS) and amino acid permease (AAP3) transporters as well as genes involved in stress response, including leucine-rich repeat receptor-like protein kinases (LRR-RLKs) were down-regulated. In addition, we found that many transcription factors associated with plant stress (such as APETALA2/ethylene response factors) were up-regulated while others (e.g., zinc-finger proteins) were down-regulated. Allelochemicals from C. canadensis also induced the up-regulation of detoxification (DTX) genes, ROS related genes, calcineurin B-like interacting protein kinases (CIPKs) and calmodulin. Overall, our findings provided insights into allelopathy in C. canadensis at the molecular level, and contributes to our understanding of invasion mechanisms of alien plant species. CLINICAL TRIALS REGISTRATION: This study does not contain any studies with clinical trials performed by any of the authors.

A novel diterpenoid, sinunanolobatone A (

ObjectivesThis phenomenological study aimed to examine intensive care unit (ICU) nurses’ experiences of caring for patients with COVID-19, and understand better their everyday experiences of patient’ management in the ICU.DesignA descriptive phenomenological research design was used. Individual interviews were conducted. The data were transcribed verbatim and analysed using Colaizzi’s seven-step framework.SettingAn ICU with 16 beds in a tertiary hospital in Wuhan, China.ParticipantsNurses who had more than 1 year of experience and had provided care to patients with COVID-19 in ICU for more than 1 week were identified as participants. A total of 13 nurses were interviewed.ResultsAn analysis of these significant statements yielded four distinct stages of feelings, thereby revealing the essence of this phenomenon. Worry about being infected and infecting family members was present across in all four stages. The themes associated with the four stages were as follows: initial contradictory feelings, quick adaption to the ‘new working environment’ in the first 1–2 weeks in the ICU, desperation after adaption, holding on and survive.ConclusionsThe nurses reported distinct experiences of providing care to patients with COVID-19 in ICUs. Interventions, such as providing information about the disease, simulation training, emotional support and follow-up care, are needed to help nurses manage patients with COVID-19 and maintain nurses’ health.

The research on the optimization of a low-carbon multimodal transportation path under uncertainty can have an important theoretical and practical significance in the high-quality development situation. This paper investigates the low-carbon path optimization problem under dual uncertainty. A hybrid robust stochastic optimization (HRSO) model is established considering the transportation cost, time cost and carbon emission cost. In order to solve this problem, a catastrophic adaptive genetic algorithm (CA-GA) based on Monte Carlo sampling is designed and tested for validity. The multimodal transportation schemes and costs under different modes are compared, and the impacts of uncertain parameters are analyzed by a 15-node multimodal transportation network numerical example. The results show that: (1) the uncertain mode will affect the decision-making of multimodal transportation, including the route and mode, (2) robust optimization with uncertain demand will increase the total cost of low-carbon multimodal transportation due to the pursuit of stability, (3) the influence of time uncertainty on the total cost is significant and fuzzy, showing the trend of an irregular wave-shaped change, like the ups and downs of the mountains. The model and algorithm we proposed can provide a theoretical basis for the administrative department and logistic services providers to optimize the transportation scheme under uncertainty.

Twenty-one dihydro-β-agarofuran derivatives were purified from the seeds of Euonymus maackii, and eight compounds (1-8) were identified as new natural products. Their structures were deduced by extensive spectroscopic analysis, X-ray diffraction studies, and comparison of observed and reported NMR data. Compounds 10, 12, 17, and 18 significantly increased the cell viability of Aβ25-35-treated SH-SY5Y cells with effects similar to that of epigallocatechin gallate (EGCG). In addition, the abundant compound 9 reduced the seizure-like locomotor activity of zebrafish at 10 μM compared with a pentylenetetrazol-treated group.

Background Nsa cytoplasmic male sterility (CMS) is a novel alloplasmic male sterility system derived from somatic hybridization between Brassica napus and Sinapis arvensis. Identification of the CMS-associated gene is a prerequisite for a better understanding of the origin and molecular mechanism of this CMS. With the development of genome sequencing technology, organelle genomes of Nsa CMS line and its maintainer line were sequenced by pyro-sequencing technology, and comparative analysis of the organelle genomes was carried out to characterize the organelle genome composition of Nsa CMS as well as to identify the candidate Nsa CMS-associated genes. Results Nsa CMS mitochondrial genome showed a higher collinearity with that of S. arvensis than B. napus, indicating that Nsa CMS mitochondrial genome was mainly derived from S. arvensis. However, mitochondrial genome recombination of parental lines was clearly detected. In contrast, the chloroplast genome of Nsa CMS was highly collinear with its B. napus parent, without any evidence of recombination of the two parental chloroplast genomes or integration from S. arvensis. There were 16 open reading frames (ORFs) specifically existed in Nsa CMS mitochondrial genome, which could not be identified in the maintainer line. Among them, three ORFs (orf224, orf309, orf346) possessing chimeric and transmembrane structure are most likely to be the candidate CMS genes. Sequences of all three candidate CMS genes in Nsa CMS line were found to be 100% identical with those from S. arvensis mitochondrial genome. Phylogenetic and homologous analysis showed that all the mitochondrial genes were highly conserved during evolution. Conclusions Nsa CMS contains a recombined mitochondrial genome of its two parental species with the majority form S. arvensis. Three candidate Nsa CMS genes were identified and proven to be derived from S. arvensis other than recombination of its two parental species. Further functional study of the candidate genes will help to identify the gene responsible for the CMS and the underlying molecular mechanism.

Abnormal protein aggregation has been linked to many neurodegenerative diseases, including Parkinson’s disease (PD). The main pathological hallmark of PD is the formation of Lewy bodies (LBs) and Lewy neurites, both of which contain the presynaptic protein alpha-synuclein (α-syn). Under normal conditions, native α-syn exists in a soluble unfolded state but undergoes misfolding and aggregation into toxic aggregates under pathological conditions. Toxic α-syn species, especially oligomers, can cause oxidative stress, membrane penetration, synaptic and mitochondrial dysfunction, as well as other damage, leading to neuronal death and eventually neurodegeneration. Early diagnosis and treatments targeting PD pathogenesis are urgently needed. Given its critical role in PD, α-syn is an attractive target for the development of both diagnostic tools and effective therapeutics. This review summarizes the progress toward discovering imaging probes and aggregation inhibitors for α-syn. Relevant strategies and techniques in the discovery of α-syn-targeted drugs are also discussed.

A new polyoxometalate-based coordination polymer, Ag2(L)2(VW12O40)][Ag2(L)2]·4H2O (1) {L = 3,5-di(1H-1,2,4-triazol-1-yl)benzoic acid}, has been isolated under hydrothermal conditions and characterized by routine methods. Compound 1 exhibits an interesting 1D + 1D polypseudo-rotaxane architecture, as shown by X-ray diffraction analysis. The new compound represents a scarce example of 1D + 1D polypseudo-rotaxane architecture, namely, ladder motifs are threaded by zigzag chains rather than a straight one. The coordination stability around loop and thread motifs was investigated to expatiate on the zigzag chained polypseudo-rotaxane. In addition, crystal 1 can be used as a packing material to selectively adsorb cationic dyes such as crystal violet (CV) and methylene blue (MB) concomitant with methyl orange anionic dyes with high uptakes and rapid adsorption rate.

Catalytic diastereo- and enantioselective hydroalkenylation of 3,3-disubstituted cyclopropenes with readily accessible alkenylboronic acids, promoted by a chiral phosphine/Co complex, is presented. Such a process constitutes the unprecedented and direct introduction of a wide range of alkenyl groups onto the cyclopropane motif to afford multisubstituted cyclopropanes in up to 95 % yield with greater than 95:5 d.r. and 99:1 e.r. Functionalization of the products delivered enantioenriched cyclopropanes that are otherwise difficult to access.

Accumulating evidence indicates the critical importance of cerebrovascular dysfunction in the pathogenesis of Alzheimer's disease (AD). However, systematic comparative studies on the precise brain vasculature of wild-type and AD model mice are still rare. Using an image-optimization method for analysing Micro-Optical Sectioning Tomography (MOST) data, we generated cross-scale whole-brain 3D atlases that cover the entire vascular system from large vessels down to smallest capillaries at submicron resolution, for both wild-type mice and a transgenic (APP/PS1) mouse model of AD. In addition to distinct vascular patterns in different brain regions, we found that the main vessels of the molecular layer of the hippocampal dentate gyrus (DG-ml) undergo abrupt changes in both diameter and branch angle, spreading a unique comb-like pattern of capillaries. By using a quantitative analysis workflow, we identified in the hippocampus of AD mice an overall reduction of the mean vascular diameter, volume fraction and branch angle, with most significant impairment in the DG-ml. In addition, virtual endoscopy revealed irregular morphological features in the vessel lumen of the AD mice, potentially contributing to the impairment of blood flow. Our results demonstrate the capability of high-resolution cross-scale evaluation of brain vasculature and underscore the importance of studying hippocampal microcirculation for understanding AD pathogenesis.

The study investigates the feasibility of the Lamb wave topological imaging method for detecting multiple blindholes in an isotropic plate. The topological imaging method is performed based on the computations of two wave fields, a forward and an adjoint, in the defect-free reference medium using different emitting sources. The image is computed by multiplying the forward and adjoint wave fields together and integrating them over time or frequency. The interferences of multimode aliasing and the scattering effect can thus be eliminated at the defectfree positions with an improved image resolution. To investigate the physical mechanism, the refocusing process of the multimode Lamb waves at the defect positions is presented by a face-to-face comparison between the snapshots of the forward and adjoint wave fields using the finite element simulation. The Lamb wave topological imaging method is numerically and experimentally verified to identify multiple blind-holes in an isotropic aluminium plate. The results demonstrate that the topological imaging method enables the suppression of the sartefacts resulting from the mode conversion and achieve high-resolution imaging of the blind defects

Aims and objectives To validate the Chinese version of the Critical-Care Pain Observation Tool (CPOT) in nonintubated and intubated ICU patients. Background While CPOT was found to have the best psychometric properties among objective pain assessment scales, there is no Chinese version CPOT for nonintubated patients. Design Cross-sectional design was used in these two observational studies. Methods Seventy-six nonintubated patients and 53 intubated patients were assessed to examine internal consistency, criterion-related and discriminative validity of CPOT in the first study. Pain assessment during low pain condition as well as increased pain condition was performed by Numeric Rating Scale (NRS) and the Chinese version COPT. Forty nonintubated patients and 43 intubated patients were assessed to examine inter-rater reliability in the second study. A bedside nurse and a researcher independently executed paired pain assessments with CPOT in the same conditions. The STROBE Statement was followed to guide these studies. Results The Cronbach's α in nonintubated patients and intubated patients was 0.903-0.930 and 0.868-0.870. The intraclass correlation coefficients (ICCs) in nonintubated patients ranged from 0.959-0.982, and the ICC in intubated patients ranged from 0.947-0.959, confirming the inter-rater reliability. The moderately positive Pearson's correlations between CPOT and NRS scores (r = 0.757-0.838 in nonintubated patients, r = 0.574-0.705 in intubated patients) indicated the criterion-related validity. A significant increase in CPOT scores in the increased pain condition compared with those acquired in the low pain condition verified the discriminative validity. Conclusions The Chinese version of CPOT was presented to be valid and reliable for both nonintubated and intubated critically ill adults, which could be applicable for pain assessment in patients in ICU. Relevance to clinical practice This study provides an applicable pain assessment tool for both nonintubated patients and intubated patients in ICU.

Increasing evidence suggests that there is a correlation between type 2 diabetes mellitus (T2D) and Alzheimer’s disease (AD). Increased Aβ polypeptide production in AD patients would promote metabolic abnormalities, insulin signaling dysfunction and perturbations in glucose utilization, thus leading to the onset of T2D. However, the metabolic mechanisms underlying the interplay between AD and its diabetes-promoting effects are not fully elucidated. Particularly, systematic metabolomics analysis has not been performed for the pancreas tissues of AD subjects, which play key roles in the glucose metabolism of living systems. In the current study, we characterized the dynamic metabolic profile alterations of the serum and the pancreas of APP/PS1 double-transgenic mice (an AD mouse model) using the untargeted metabolomics approaches. Serum and pancreatic tissues of APP/PS1 transgenic mice and wild-type mice were extracted and subjected to NMR analysis to evaluate the functional state of pancreas in the progress of AD. Multivariate analysis of principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were conducted to define the global and the local (pancreas) metabolic features associated with the possible initiation of T2D in the progress of AD. Our results showed the onset of AD-induced global glucose metabolism disorders in AD mice. Hyperglycemia and its accompanying metabolic disorders including energy metabolism down-regulation and oxidative stress were observed in the serum of AD mice. Meanwhile, global disturbance of branched-chain amino acid (BCAA) metabolism was detected, and the change of BCAA (leucine) was positively correlated to the alteration of glucose. Moreover, increased level of glucose and enhanced energy metabolism were observed in the pancreas of AD mice. The results suggest that the diabetes-promoting effects accompanying the progress of AD are achieved by down-regulating the global utilization of glucose and interfering with the metabolic function of pancreas. Since T2D is a risk factor for the pathogenesis of AD, our findings suggest that targeting the glucose metabolism dysfunctions might serve as a supplementary therapeutic strategy for Alzheimer’s disease.

Portulaca oleracea, a plant species used as medicine and food, is widely spread in most areas of China. It is also a popular food in some Europe and Mediterranean countries. Purslane contains a variety of chemical constituents with pharmacological activities, such as antitumor, hypoglycemic, antioxidant, antibacterial, anti-inflammatory activities. It is also full of plenty of nutrients serving as a diet food or healthy food. Here we reviewed purslane in the following aspects: botanical resources, ethnopharmacological function, chemical constituents, pharmacology and pharmacokinetics, safety evaluation and toxicity, and clinical applications.

Two new sesquiterpene pyridine alkaloids, Chinese bittersweet alkaloid A (1) and Chinese bittersweet alkaloid B (2), together with five known compounds 3β- hydroxyolean-9(11),12-diene, β-si...

Based on SPME‐GC‐MS analysis, it could be found that the production of acetic acid, phenethyl acetate, and isoamyl acetate gradually increased in the apple vinegar fermentation broth with the fermentation time. Consequently, in order to systematically explore the dynamic changes of microbial diversity and metabolites in the process of apple vinegar fermentation, 16S rDNA were sequenced and analyzed in this work. The present results showed that bacterial diversity was rich and exhibited a certain variation during the dynamic fermentation process of apple vinegar. Furthermore, Lactococcus and Oenococcus were the predominant bacteria in the pre‐fermentation (alcoholic fermentation) of apple vinegar, while the dominant bacteria in the middle and late fermentation stages (acetic acid fermentation) were Lactococcus and Acetobacter. In addition, during the whole fermentation process of apple vinegar, Lactococcus was the most dominant bacteria, Oenococcus was the unique species in the stage of alcohol fermentation, and Acetobacter increased rapidly in the stage of acetic acid fermentation. In conclusion, our finding provided a theoretical basis for the processing technology of apple vinegar fermentation, and a theory evidence for the safety and health assessment of apple vinegar.

BACKGROUND Cervical lymph node metastasis in papillary thyroid carcinoma (PTC) affects the treatment and prognosis of patients. Ultrasound is a common imaging method for detecting cervical lymph nodes in PTC patients; however, it is not accurate in determining lymph node metastasis. AIM To evaluate the value of contrast-enhanced ultrasound combined with elastography in evaluating cervical lymph node metastasis in PTC. METHODS A total of 94 patients with PTC were recruited. According to pathological results, lymph nodes were divided into two groups: metastatic group (n = 50) and reactive group (n = 63). The routine ultrasound findings, contrast-enhanced ultrasound and elastography data were recorded and compared. Logistic regression was used to generate predictive probability distributions for the diagnosis of lymph node metastasis with different indicators. Receiver operating characteristic curve analysis was used to test the efficacy of contrast-enhanced ultrasound combined with elastography based on routine ultrasound in evaluating PTC cervical lymph node metastasis. RESULTS The ratio of long diameter/short diameter (L/S) ≤ 2, irregular marginal morphology, missing lymphatic portal, peripheral or mixed blood flow distribution, peak intensity (PI), non-uniform contrast distribution and elasticity score in the metastatic group were significantly higher than those in the reactive group (P < 0.05). L/S ratio, missing lymphatic portal, PI and elasticity score had a significant influence on the occurrence of PTC cervical lymph node metastasis (P < 0.05). Furthermore, the area under the curve (AUC) for lymph node metastasis diagnosed using the combination of PI ratio, elasticity score, missing lymphatic portal and LS was 0.936, which was significantly higher than the AUC for PI ratio alone. The difference was statistically significant (P < 0.05). The fitting equation for the combined diagnosis was logit(P) = -12.341 + 1.482 × L/S ratio + 3.529 × missing lymphatic portal + 0.392 × PI + 3.288 × elasticity score. CONCLUSION Based on the gray-scale ultrasound, the combination of contrast-enhanced ultrasound and elastography can accurately assess PTC cervical lymph node metastasis.

Primary dysmenorrhea is a common disease among females in their reproductive age and adolescents. The main complaint is lower abdominal pain during menstruation. Females, who suffer from dysmenorrhea, widely use nonsteroidal anti-inflammatory drugs that reduce muscle spasm by inhibiting prostaglandin synthesis and vasopressin secretion. However, there are side effects when patients take them for a long time. It is therefore against this backdrop that herbal medicines are suggested as an alternative source of treatment for primary dysmenorrhea. In this paper, a review of studies demonstrating the relieving of uterine contraction and reduction in prostaglandin synthesis by alternative sources such as traditional Chinese medicines (TCM) is spelt out. TCM conceptualizes that, menstrual pain resulting from qi is due to stagnated and retained blood. Blood deficiency and coldness in the whole human body are two additional causes of dysmenorrhea. Therefore, based on these, the main focus of treatment is directed at relieving the above symptoms. Chinese herbal prescriptions exert their effects through these mechanisms: prostaglandin reduction, inhibition of cyclooxygenase, intracellular Ca2+, and nitric oxide, declining malondialdehyde, and reverse increasing superoxide dismutase. Hence, Chinese herbal prescriptions, present perhaps a more beneficial efficacious alternative in the treatment of primary dysmenorrhea, more especially in the confines of complementary and alternative medicine.

A novel norditerpenoid, sinusiaetone A (

Objective: To screen and analyze the function of specific circular RNA involved of pathological bone formation in ankylosing spondylitis. Methods: From September 2019 to October 2020, Ossification capsule of 3 patients with ankylosing spondylitis developed hip joint fusion and capsule of 3 patients with femoral neck fracture were enrolled as the experimental group and the control group, respectively. The circular RNA expressions of hip capsule were analyzed by arraystar circRNA chip, bioinformatics analyses including the circRNA/miRNA/mRNA interaction network, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis.Results: The results showed that there totally were 25 up-regulated and 39 down-regulated differential circRNAs, among these circRNAs,we screened most up-regulated 10 circRNAs and most down-regulated 13 circRNAs in ankylosing spondylitis (FC≥2,P＜0.05). Further analysis demonstrated that two signal ways were most involved and correslated with the different circRNAs-“Focal Adhesion signal pathway” and “Rap1 signal pathway” Conclusion: The circular RNAs involved of pathological bone formation in ankylosing spondylitis were significantly different from that of the control group. These differentially expressed circular RNAs may be closely related to the occurrence and development of pathological bone formation in ankylosing spondylitis. Key words: CircRNA, Ankylosing spondylitis, Gene chip, Pathological bone formation

Three new sesquiterpene polyol ester compounds angulatins S-U, together with three known compounds were isolated from

Based on a multitarget strategy, a series of novel tacrine-pyrimidone hybrids were identified for the potential treatment of Alzheimer's disease (AD). Biological evaluation results demonstrated that these hybrids exhibited significant inhibitory activities toward acetylcholinesterase (AChE) and glycogen synthase kinase 3 (GSK-3). The optimal compound 27g possessed excellent dual AChE/GSK-3 inhibition both in terms of potency and equilibrium (AChE: IC50 = 51.1 nM; GSK-3β: IC50 = 89.3 nM) and displayed significant amelioration on cognitive deficits in scopolamine-induced amnesia mice and efficient reduction against phosphorylation of tau protein on Ser-199 and Ser-396 sites in glyceraldehyde (GA)-stimulated differentiated SH-SY5Y cells. Furthermore, compound 27g exhibited eligible pharmacokinetic properties, good kinase selectivity, and moderate neuroprotection against GA-induced reduction in cell viability and neurite damage in SH-SY5Y-derived neurons. The multifunctional profiles of compound 27g suggest that it deserves further investigation as a promising lead for the prospective treatment of AD.

FPS-ZM1 is an inhibitor of the receptor for advanced glycation end products (RAGE). Nevertheless, there are few reports about its direct effects on microglial inflammation, and the underlying molecular mechanisms remain to be clarified. The present study investigated the potential effects of FPS-ZM1 on lipopolysaccharide (LPS)-mediated microglial inflammation both in vivo and in vitro, and further elucidated the possible molecular mechanisms of action. FPS-ZM1 decreased LPS-induced overproduction of interleukin-1 beta (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and cyclooxygenase 2 (COX-2), in both BV-2 cells and primary microglial cells. FPS-ZM1 (10 mg/kg, i.p.) ameliorated proliferation and activation of microglia in the hippocampus of C57BL/6J mice subjected to LPS challenge (5 mg/kg, i.p.). Meanwhile, overproduction of pro-inflammatory cytokines IL-1β and TNF-α in the hippocampus was alleviated after treatment with FPS-ZM1. RNA-Sequencing (RNA-Seq) analysis showed involvement of Janus kinase (JAK)-signal transducers and activators of transcription (STAT) signaling pathway in the regulation of FPS-ZM1 on LPS-induced microglial inflammation. Further investigations demonstrated that FPS-ZM1 downregulated LPS-mediated increases in the phosphorylation levels of JAK/STAT both in vivo and in vitro. FPS-ZM1 also suppressed the nuclear translocation of transcription factor STAT1/3/5 in BV-2 cells. In addition, inhibition of JAK/STAT signaling pathway had an anti-inflammatory effect similar to FPS-ZM1 treatment. Taken together, our results verified the inhibitory effects of FPS-ZM1 against LPS-stimulated microglial inflammation, and for the first time demonstrated such anti-inflammatory activities on microglia are associated with regulation of JAK/STAT signaling pathway both in vivo and in vitro, which may shed new light on the pharmacological mechanisms of FPS-ZM1 against microglial inflammation.

Two eudesmane-guaiane/lindenane heterocoupled sesquiterpenoid dimers, horienoids A (

Real-time non-destructive monitoring of water use efficiency (WUE) is important for screening high-yielding high-efficiency varieties and determining the rational allocation of water resources in winter wheat production. Compared with vertical observation angles, multi-angle remote sensing provides more information on mid to lower parts of the wheat canopy, thereby improving estimates of physical and chemical indicators of the entire canopy. In this study, multi-angle spectral reflectance and the WUE of the wheat canopy were obtained at different growth stages based on field experiments carried out across 4 years using three wheat varieties under different water and nitrogen fertilizer regimes. Using appropriate spectral parameters and sensitive observation angles, the quantitative relationships with wheat WUE were determined. The results revealed that backward observation angles were better than forward angles, while the common spectral parameters Lo and NDDAig were found to be closely related to WUE, although with increasing WUE, both parameters tended to become saturated. Using this data, we constructed a double-ratio vegetation index (NDDAig/FWBI), which we named the water efficiency index (WEI), reducing the impact of different test factors on the WUE monitoring model. As a result, we were able to create a unified monitoring model within an angle range of −20–10°. The equation fitting determination coefficient (R2) and root mean square error (RMSE) of the model were 0.623 and 0.406, respectively, while an independent experiment carried out to test the monitoring models confirmed that the model based on the new index was optimal, with R2, RMSE, and relative error (RE) values of 0.685, 0.473, and 11.847%, respectively. These findings suggest that the WEI is more sensitive to WUE changes than common spectral parameters, while also allowing wide-angle adaptation, which has important implications in parameter design and the configuration of satellite remote sensing and UAV sensors.

Due to the redox properties closely related to numerous physiological and pathological processes, biothiols, including cysteine (Cys), homocysteine (Hcy) and glutathione (GSH), have received considerable attention in biological science. On account of the important physiological roles of these biothiols, it is of profound significance to develop sensitive and selective detection of biothiols to understand their biological profiles. In this work, we reported an efficient fluorescent probe, PHPQ-SH, for detecting biothiols in vitro and vivo, based on the phenothiazine-HPQ skeleton, with DNBS (2,4-dinitrobenzenesulfonate) as the response unit. Probe PHPQ-SH exhibited brilliant sensing performances toward thiols, including a large Stokes shift (138 nm), excellent sensitivity (for GSH, LOD = 18.3 nM), remarkable fluorescence enhancement (163-fold), low cytotoxicity, rapid response (8 min), and extraordinary selectivity. Finally, the probe PHPQ-SH illustrated herein was capable of responding and visualizing biothiols in MCF-7 cells and zebrafish.

To explore the diagnostic value of HBA1 178 couples in the department of women's health of Chongqing maternal and child health hospital were selected for pregnancy examination. Peripheral venous blood was extracted and analyzed for parallel blood routine test, hemoglobin capillary electrophoresis and thalassemia gene detection.A total of 265 cases of thalassemia gene carriers were screened out in 1 178 couples； 91.3% βHBAHBA通过分析血红蛋白A2（HBA选取重庆市妇幼保健院妇女保健科1 178对孕前检查夫妇，抽取外周静脉血，进行平行的血常规检查、血红蛋白电泳和地中海贫血基因的检测与分析.1 178对夫妇共筛查出265例地中海贫血基因携带者；以HBAHBA

The chemical investigation of the South China Sea soft coral

PurposeTo validate the 8th edition of the American Joint Committee on Cancer (AJCC) pathological prognostic staging system for breast cancer patients with internal mammary lymph nodes (IMN) metastasis (N3b disease, stage IIIC in 7th AJCC anatomical staging).MethodsBreast cancer patients with IMN metastasis diagnosed between 2010 and 2014 were retrieved from the Surveillance, Epidemiology, and End Results program. Chi-squared test, Log-rank test, Kaplan-Meier method, and Cox proportional hazard analysis were applied to statistical analysis.ResultsWe included 678 patients with N3b disease in this study. Overall, 68.4% of patients were downstaged to IIIA and IIIB diseases from the 7th anatomical staging to 8th pathological prognostic staging. The new pathological prognostic staging system had better discriminatory value on prognosis prediction among IMN-metastasized breast cancer patients, with a 5-year breast cancer-specific survival (BCSS) of 92.7, 77.4, and 66.0% in stage IIIA, IIIB, and IIIC diseases, respectively (PConclusionThe 8th AJCC pathological prognostic staging system offers more refined prognostic stratification to IMN-metastasized breast cancer patients and endorses its use in routine clinical practice for this specific subgroup of breast cancer.

A precise transit ephemeris serves as the premise for follow-up exoplanet observations. We compare TESS Objects of Interest (TOI) transit timings of 262 hot Jupiters with the archival ephemeris and find 31 of them having TOI timing offsets, among which WASP-161b shows the most significant offset of -203.7$\pm$4.1 minutes. The median value of these offsets is 17.8 minutes, equivalent to 3.6 $\sigma$. We generate TESS timings in each sector for these 31 hot Jupiters, using a self-generated pipeline. The pipeline performs photometric measurements to TESS images and produces transit timings by fitting the light curves. We refine and update the previous ephemeris, based on these TESS timings (uncertainty $\sim$ 1 minute) and a long timing baseline ($\sim 10$ years). Our refined ephemeris gives the transit timing at a median precision of 0.82 minutes until 2025 and 1.21 minutes until 2030. We regard the timing offsets mainly originating from the underestimated ephemeris uncertainty. All the targets with timing offset larger than 10$\sigma$ present earlier timings than the prediction, which cannot be due to underestimated ephemeris uncertainty, apsidal precision, or R$\o$mer effect as those effects should be unsigned. For some particular targets, timing offsets are likely due to tidal dissipation. Our sample leads to the detection of period decaying candidates of WASP-161b and XO-3b reported previously., Comment: Submitted to ApJS; 24 pages

Three new dimeric diarylheptanoids, taccachanfurans A-C (

Void defects under track slabs are the main danger affecting the safe operation of high-speed railways. In the short high-speed railway maintenance periods, China’s high-speed railway line maintenance operations must quickly and dynamically determine void defects under track slabs that are in service without contact. However, the detection of void defects under track slabs still mainly relies on the manual inspection and flaw detection by railway workers during the railway maintenance period. If the defects are not quickly identified, the consequences could be disastrous. This article presents a new method for the non-contact dynamic detection of void defects under track slabs. The method involves the use of air-coupled ultrasonic sensors to generate and receive ultrasonic guided waves in the track slab to quantitatively represent the size of the void defect according to the principle of energy leakage of guided waves in the propagation process. The characteristics of the position-amplitude curve, taking the position of the beam axis as the abscissa and the amplitude of the time domain signal as the ordinate, were numerically calculated and analyzed. The quantitative relationship between the convex interval of the position-amplitude curve and the size of the void defect was obtained, and an imaging method of the void defects based on x, y two-dimensional line scanning data fusion is proposed. The excitation and reception methods of air-coupled ultrasonic guided waves were studied, and a 1:1 model of the track structure was built in the laboratory to verify the method and detect the void defect under the track slab. The experimental results show that ultrasonic guided waves can be excited and received in the track slab by air-coupled ultrasonic sensors. Based on the guided wave energy leakage principle, the quantitative characterization and imaging of the void defect under track slabs can be realized.

28-O-caffeoyl betulin (B-CA) has been demonstrated to reduce the cerebral infarct volume caused by transient middle cerebral artery occlusion (MCAO) injury. B-CA is a novel derivative of naturally occurring caffeoyl triterpene with little information associated with its pharmacological target(s). To date no data is available regarding the effect of B-CA on brain metabolism. In the present study, a 1H-NMR-based metabolomics approach was applied to investigate the therapeutic effects of B-CA on brain metabolism following MCAO in rats. Global metabolic profiles of the cortex in acute period (9 h after focal ischemia onset) after MCAO were compared between the groups (sham; MCAO + vehicle; MCAO + B-CA). MCAO induced several changes in the ipsilateral cortex of ischemic rats, which consequently led to the neuronal damage featured with the downregulation of NAA, including energy metabolism dysfunctions, oxidative stress, and neurotransmitter metabolism. Treatment with B-CA showed statistically significant rescue effects on the ischemic cortex of MCAO rats. Specifically, treatment with B-CA ameliorated the energy metabolism dysfunctions (back-regulating the levels of succinate, lactate, BCAAs, and carnitine), oxidative stress (upregulating the level of glutathione), and neurotransmitter metabolism disturbances (back-regulating the levels of γ-aminobutyric acid and acetylcholine) associated with the progression of ischemic stroke. With the administration of B-CA, the levels of three phospholipid related metabolites (O-phosphocholine, O-phosphoethanolamine, sn-glycero-3-phosphocholine) and NAA improved significantly. Overall, our findings suggest that treatment with B-CA may provide neuroprotection by augmenting the metabolic changes observed in the cortex following MCAO in rats.

To investigate the prevalence and gene distribution of thalassemia among people at reproductive age in yuzhong district, Chongqing.1000 pre -pregnancy examination couples in yuzhong district were investigated. Peripheral venous blood was extracted and next-generation sequencing was used to screen the thalassemia genes.Among the 1000 pregnant couples, the thalassemia gene carrying rate was 7.45%, the carrying rate of α and β thalassemia genes were 4.60% and 2.10%, respectively. The most common α thalassemia genotypes in αα/-α3.7 (53.26%), αα/--SEA (23.91%), αα/-α4.2 (11.96%); and the most common genotypes in β thalassemia genotypes were mainly Codons17 (A＞T) (26.19%)、Condon41/42 (-TTCT) (26.19%)、IVS-II-654 (C＞T) (14.29%) At the same time, 3 cases of α and β complex thalassemia and 3 pairs of homotypic thalassemia genes were detected, more over, 12 cases of 5 new genes were found.Yuzhong district of Chongqing is a high incidence area of thalassemia, and the diversity of gene mutation types is relatively rich. Screening for thalassemia before pregnancy is of great significance to improve the quality of population.基于高通量测序技术的重庆市渝中区育龄人群地中海贫血流行病调查及基因分析.调查重庆市渝中区育龄人群地中海贫血携带率，了解本地区地中海贫血基因的分布.对重庆渝中区1000对孕前检查夫妇进行调查，抽取外周静脉血，采取高通量测序技术进行地中海贫血基因的筛查.1000对孕前检查夫妇中，地中海贫血基因携带率为7.45%，α地中海贫血基因携带率为4.60%，β地中海贫血基因携带率为2.10%。其中α地中海贫血基因型主要为αα/-α3.7（53.26%）、αα/--SEA（23.91%）、αα/-α4.2（11.96%）；β地中海贫血基因型主要为Codons17（A＞T）（26.19%）、Condon41/42（-TTCT）（26.19%）、IVS-II-654（C＞T）（14.29%）。同时，检测出3例α、β复合型地中海贫血，3对同型地中海贫血基因夫妇，新发现基因5种12例.重庆市渝中区为地中海贫血高发区，基因突变类型较为多样，在孕前对备孕夫妇进行地中海贫血筛查，对提高出生人口质量有重要的意义.